Investigating the functions and therapeutic potential for Eph receptors and ephrins during wound repair and inflammation

研究 Eph 受体和肝配蛋白在伤口修复和炎症过程中的功能和治疗潜力

• 批准号: G0901822/1
• 负责人: Paul Martin
• 金额: $ 74.3万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901822%2F1
• 关键词: Investigating; functions; therapeutic; potential; Eph

Wound healing is the body?s process of repairing damaged tissue and takes place for all wounds, be they a nick to the finger or the repair of internal organs after abdominal surgery. There are many occasions when tissue repair fails, leading to chronic non-healing wounds such as venous leg ulcers which are a huge clinical burden for elderly patients and suffered by about 500,000 people in the UK. Equally, the process can be too exuberant leading to fibrosis and scarring as a consequence of excessive contraction, healing and inflammation. In order to understand how tissue repair goes awry and how it might be improved, we need to better understand the process, and essentially that means figuring out how the dormant tissues of unwounded skin (or other organs), are awakened upon damage, allowing them to migrate and fill the gap created by the wound, and how they know when to stop when the wound is healed.The studies outlined here are to investigate a family of receptors and the proteins that bind to them, the Ephs and ephrins, that, despite being very well studied in embryonic development and in cancer and implicated in regulating the ?starting and stopping? of cell migrations in both these scenarios, have not previously been studied in the wound repair process. We have preliminary data in mouse that shows how several members of this large family of receptors become expressed and activated in particular cell types during the wound closure process, in ways that are suggestive of their being key players, and we will look to see whether the same is true in human wound tissues and whether biopsies from pathological wounds, in particular longstanding leg ulcers, have an altered pattern of these receptors. We will then test whether modulating particular Eph family members will allow us to alter and improve some aspects of healing while not affecting others, with a view to designing therapies that can either ?kickstart? the tissues of a non-healing wound to repair itself or shut down the repair machinery in a wound that is too inflamed and/or too exuberant and likely to form a bad scar.

伤口愈合是修复受损组织的身体的过程，并发生在所有伤口上，无论是手指的痕迹还是腹部手术后内部器官的修复。在许多情况下，组织修复发生故障，导致慢性非愈合伤口，例如静脉腿溃疡，这对老年患者来说是巨大的临床负担，在英国大约有50万人遭受了约50万人的痛苦。同样，由于收缩过度，愈合和炎症，该过程可能会导致纤维化和疤痕。为了了解组织修复如何出现问题以及如何改进，我们需要更好地理解过程，从本质上讲，这意味着要弄清楚未造成的皮肤（或其他器官）的休眠组织如何受到损害，在伤害下唤醒，从而使它们迁移并填补伤口所产生的间隙，以及在这里何时会在伤口中遇到何时会导致受伤的研究。埃弗斯（Ephs）和埃弗林（Ephs），尽管在胚胎发育和癌症方面对其进行了很好的研究，并涉及调节？开始和停止？在这两种情况下，细胞迁移的迁移，以前尚未在伤口修复过程中研究。我们在鼠标中拥有初步数据，该数据显示了在伤口闭合过程中，该大型受体家族的几个成员在特定的细胞类型中如何表达和激活，以暗示它们是关键参与者的方式，我们将看到人伤口组织中的活检和病理伤口中是否是相同的。然后，我们将测试调节特定的EPH家庭成员是否会使我们能够改变和改善康复的某些方面，同时不影响其他方面，以设计可以启动的疗法？无愈合的伤口组织以修复自身或关闭伤口中的修复机械，该伤口太发炎和/或过于旺盛，可能会形成不良的疤痕。